The Next Biotech Harvest

The Next Biotech Harvest

for the next few years, large-scale production of plastic will remain in the factory, not the field. Even in DuPont’s most advanced research projects for plant-based materials, Ireland concedes, scientists are still “unraveling the enzymatic pathways while simultaneously developing all the polymer chemistry. No one really understands how to control and regulate plant gene expression.”

But if plant genomics continues to accelerate at its current rate, it may become far easier to reach that goal. Most common crops have a large amount of DNA and about 50,000 genes-roughly half the number in humans. But using fast, automated machines honed for unraveling the human genome, plant geneticists are identifying genes more quickly than botanists know how to cultivate them.

Scott Tingey, director of DuPont’s genomics program, says technology has had a profound impact on the field. “A few years ago, it took two man-years to clone a plant gene,” Tingey says. “About half the time you were successful, the other half you fell on your face. Today, life is very different.” Over the last two years, DuPont has created a database of DNA sequences for corn, soybeans, wheat and rice. “It eliminates the tedious gene discovery process. That’s no longer the rate-limiting step in a project,” explains Tingey.

Biologists anticipate completing the sequencing of Arabidopsis (a weed that is the primary genetic model for plant genetics) by 2000, as a result of an international collaboration that began in 1989. That could be crucial because all flowering plants have essentially the same set of genes. “Within the next five years, we’ll know the function of all plant genes at some level,” predicts Stanford’s Somerville. “It’s a major change. We’ll be in a lot better position to make rational improvements in plants.”

Back at newly formed Cereon, one goal is to turn the sequencing of interesting genetic material into a routine, high-throughput production line. In particular, the company wants to accelerate the process of finding a DNA sequence responsible for a specific phenotype, or physical trait. “We are setting up systems that will allow molecular geneticists to go from a phenotype of interest to having a cloned gene, and knowing the sequence for that trait, in a very short time,” says Cereon president William Timberlake. “It now takes years to get at some of these genes,” Timberlake explains. “We would like to reduce that to weeks or months.”

But gathering all that gene information is only the first step. Oliver Peoples, co-founder of Metabolix, explains: “What do you do with all the gene information from genomics? You begin to engineer pathways to optimize the flow of carbon. It’s the end use of genomics-it’s the ultimate jigsaw puzzle.” In other words, the dream is to control the entire metabolism of a plant.

Companies intent on turning crop plants into factories are working on some preliminary steps. DuPont intends to sharpen its biology skills by making a plastic intermediate from sugar using genetically engineered microbes in a fermentation process. The intermediate is the key ingredient in a novel polymer that could compete with nylon, and the company plans to have a small-scale production facility up and running by late 2000. It will be DuPont’s first attempt at a biologically based production process, and, says Dorsch, it will guide the company’s plans for using biology to make materials.

Against one wall of Dorsch’s office is a diagram mapping the metabolic pathways in a bacterium. It resembles a chemical engineering flow diagram-the kind you see everywhere at DuPont-only it’s far more complex. The idea, Dorsch says, is to take advantage of the natural flows of carbon in the organism and to engineer subtle changes that allow you to siphon off a desired product. “Organisms are already tuned up to work very well. If you try to move a significant fraction of the carbon through a different pathway, you are getting toward having to completely re-engineer the beast. I don’t think we’re so audacious as to believe that that is something that will happen any time soon.” He quickly adds, “But we might get there.”

The DuPont research labs on the outskirts of Wilmington, Del., are sacred ground for polymer scientists and chemists. They are ground zero for modern American industrial chemistry, the place where nylon was invented. And petroleum-based chemistry has long reigned here. Now, says Ireland, biology is “revitalizing” the research. “The polymer chemists are excited about it because they see the possibilities inherent in the science. The biologists are excited because they see the opportunity to use their talents to make a lot of money for the company.”

Towering distillation columns are still more common than cornfields in Wilmington. But if DuPont and its rivals are successful, the gap between the agricultural markets and the chemical industry could soon be about to close. Indeed, the gap between industrial chemistry and biology already has.